DEC-205 is a cell surface receptor for CpG oligonucleotides
Mireille H Lahoud, Fatma Ahmet, Jian-Guo Zhang, Simone Meuter, Antonia N Policheni, Susie Kitsoulis, Chin-Nien Lee, Meredith O'Keeffe, Lucy C Sullivan, Andrew G Brooks, Richard Berry, Jamie Rossjohn, Justine D Mintern, Javier Vega-Ramos, Jose A Villadangos, Nicos A Nicola, Michel C Nussenzweig, Katryn J Stacey, Ken Shortman, William R Heath Show all
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2012
Synthetic CpG oligonucleotides (ODN) have potent immunostimulatory properties exploited in clinical vaccine trials. How CpG ODN are captured and delivered to the intracellular receptor TLR9, however, has been elusive. Here we show that DEC-205, a multilectin receptor expressed by a variety of cells, is a receptor for CpG ODN. When CpG ODN are used as an adjuvant, mice deficient in DEC-205 have impaired dendritic cell (DC) and B-cell maturation, are unable to make some cytokines such as IL-12, and display suboptimal cytotoxic T-cell responses. We reveal that DEC-205 directly binds class B CpG ODN and enhances their uptake. The CpG-ODN binding function of DEC-205 is conserved between mouse and..View full abstract
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Awarded by National Health and Medical Research Council of Australia (NHMRC)
Awarded by NHMRC
We thank Belinda Phipson for her advice on statistical analysis. This work was supported by the National Health and Medical Research Council of Australia (NHMRC) Program Grants 454465 (to K. S. and W. R. H.) and 461269 (to N.A.N. and J.-G.Z.); NHMRC Project Grants 575546 (to K. S., M. H. L., and I. C.), 1003355 (to W. R. H. and I. C.), 461254 (J.A.V.), 461255 (to J.A.V.), and 637362 (to J.A.V.); and Australian Research Council Federation Fellowship (to W. R. H.). S. M. was supported by the Swiss National Science Foundation, and J.D.M. and L. C. S. are the recipients of NHMRC Career Development Awards. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme.